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Phase 2 Trial of Adagrasib Monotherapy and in Combination With Pembrolizumab and a Phase 3 Trial of Adagrasib in Combination in Patients With a KRAS G12C Mutation KRYSTAL-7
Trial Status: active
The Phase 2 portion of this study evaluates the efficacy and safety of MRTX849
monotherapy and in combination with pembrolizumab in cohorts of patients with advanced
NSCLC with KRAS G12C mutation and any PD-L1 TPS and who are candidates for first-line
treatment.
The Phase 3 portion of the study compares the efficacy of adagrasib in combination with
pembrolizumab versus pembrolizumab in patients with unresectable, locally advanced or
metastatic squamous or nonsquamous NSCLC with KRAS G12C mutation and PD-L1 TPS >=50% and
who are candidates for first line treatment.
Inclusion Criteria
Phase 2: Histologically confirmed diagnosis of unresectable or metastatic NSCLC with KRAS G12C mutation and any PD-L1 TPS
Phase 3: Histologically confirmed diagnosis of unresectable or metastatic squamous or nonsquamous NSCLC with KRAS G12C mutation and PD-L1 TPS>=50%
Phase 3: Presence of measurable disease per RECIST1.1
Phase 3: CNS Inclusion - Based on screening brain imaging, patients must have one of the following:
No evidence of brain metastases
Untreated brain metastases not needing immediate local therapy
Previously treated brain metastases not needing immediate local therapy
Exclusion Criteria
Phase 2 and Phase 3: Prior systemic treatment for locally advanced or metastatic NSCLC including chemotherapy, immune checkpoint inhibitor therapy, or a therapy targeting KRAS G12C mutation (e.g., AMG 510).
Phase 2: Active brain metastases
Phase 3: Patients with known central nervous system (CNS) lesions must not have any of the following:
Any untreated brain lesions > 2.0 cm in size
Any brainstem lesions
Ongoing use of systemic corticosteroids for control of symptoms of brain lesions at a total daily dose of > 10 mg of prednisone (or equivalent) prior to randomization.
Have poorly controlled (> 1/week) generalized or complex partial seizures, or manifest neurologic progression due to brain lesions notwithstanding CNS-directed therapy
Phase 3: Radiation to the lung > 30 Gy within 6 months prior to the first dose of study treatment
Study sponsor and potential other locations can be found on ClinicalTrials.gov for NCT04613596.
Locations matching your search criteria
United States
District of Columbia
Washington
MedStar Washington Hospital Center
Status: Active
Name Not Available
Illinois
Chicago
University of Chicago Comprehensive Cancer Center
Status: Active
Name Not Available
Maryland
Baltimore
Johns Hopkins University/Sidney Kimmel Cancer Center
Status: Active
Name Not Available
Massachusetts
Boston
Dana-Farber Cancer Institute
Status: Temporarily closed to accrual
Name Not Available
Beth Israel Deaconess Medical Center
Status: Approved
Name Not Available
Brigham and Women's Hospital
Status: Temporarily closed to accrual
Name Not Available
New York
Bronx
Montefiore Medical Center-Weiler Hospital
Status: Active
Name Not Available
Ohio
Cleveland
Case Comprehensive Cancer Center
Status: Active
Name Not Available
The Phase 2 portion of this study will evaluate the efficacy and safety of MRTX849 as
monotherapy and in combination with pembrolizumab. There will be 3 cohorts of patients,
all of whom have KRAS G12C mutation, have advanced or metastatic NSCLC, and are
candidates for first-line treatment. 2 cohorts have PD-L1 TPS score <1% and are
randomized to MRTX849 monotherapy or MRTX849 in combination with pembrolizumab. The 3rd
cohort has PD-L1 TPS score of 1% or higher and is treated with MRTX849 and pembrolizumab
The Phase 3 portion of the study will randomize patients with squamous or nonsquamous
NSCLC with KRAS G12C mutation and TPS >=50% in the first-line setting to adagrasib plus
pembrolizumab or pembrolizumab. Primary efficacy objective is to compare efficacy between
experimental and comparator arms. Secondary and exploratory objectives include evaluation
of secondary efficacy endpoints, safety and tolerability, adagrasib PK, PROs, and
correlative genomic biomarkers for the combination regimen in the study population.
MRTX849 is an orally available small molecule inhibitor of KRAS G12C, and Pembrolizumab
(KEYTRUDA®) is a humanized monoclonal antibody that blocks the interaction between PD-1
